JP2014158469A5 - - Google Patents

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JP2014158469A5
JP2014158469A5 JP2014043403A JP2014043403A JP2014158469A5 JP 2014158469 A5 JP2014158469 A5 JP 2014158469A5 JP 2014043403 A JP2014043403 A JP 2014043403A JP 2014043403 A JP2014043403 A JP 2014043403A JP 2014158469 A5 JP2014158469 A5 JP 2014158469A5
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antibody
antibody according
variable region
amino acid
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ヒトデルタ様リガンド4 (DLL4) (SEQ ID NO: 25) のアミノ酸217で切断されたN末端断片に特異的に結合しかつ、腫瘍成長を阻害することができる、モノクローナル抗体。A monoclonal antibody that specifically binds to an N-terminal fragment cleaved at amino acid 217 of human delta-like ligand 4 (DLL4) (SEQ ID NO: 25) and can inhibit tumor growth. ヒトDLL4 Delta-Serrated-Lag-2 (DSL) ドメイン (SEQ ID NO: 26) 内のアミノ酸を含むエピトープに結合する、請求項1記載のモノクローナル抗体。The monoclonal antibody according to claim 1, which binds to an epitope comprising an amino acid within the human DLL4 Delta-Serrated-Lag-2 (DSL) domain (SEQ ID NO: 26). アミノ酸66-73 (QAVVSPGP) を含むエピトープに結合する、請求項1または2記載の抗体。3. The antibody of claim 1 or 2, which binds to an epitope comprising amino acids 66-73 (QAVVSPGP). アミノ酸139-146 (LISKIAIQ) を含むエピトープに結合する、請求項1〜3のいずれか一項記載の抗体。The antibody according to any one of claims 1 to 3, which binds to an epitope comprising amino acids 139-146 (LISKIAIQ). アミノ酸66-73 (QAVVSPGP) および139-146 (LISKIAIQ) を含むエピトープに結合する、請求項1〜4のいずれか一項記載の抗体。The antibody according to any one of claims 1 to 4, which binds to an epitope comprising amino acids 66-73 (QAVVSPGP) and 139-146 (LISKIAIQ). ヒトDLL4に特異的に結合するモノクローナル抗体であって、A monoclonal antibody that specifically binds to human DLL4,
(a) CDRアミノ酸配列CDR1 (SEQ ID NO: 1)、CDR2 (SEQ ID NO: 2、SEQ ID NO: 3、またはSEQ ID NO: 4)、およびCDR3 (SEQ ID NO: 5) を含む、重鎖可変領域、ならびに(a) A heavy chain comprising CDR amino acid sequences CDR1 (SEQ ID NO: 1), CDR2 (SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4), and CDR3 (SEQ ID NO: 5). The chain variable region, and
(b) CDRアミノ酸配列CDR1 (SEQ ID NO: 9)、CDR2 (SEQ ID NO: 10)、およびCDR3 (SEQ ID NO: 11) を含む、軽鎖可変領域(b) Light chain variable region comprising CDR amino acid sequences CDR1 (SEQ ID NO: 9), CDR2 (SEQ ID NO: 10), and CDR3 (SEQ ID NO: 11)
を含み、腫瘍成長を阻害することができる、モノクローナル抗体。And a monoclonal antibody capable of inhibiting tumor growth. ヒトDLL4に特異的に結合するモノクローナル抗体であって、A monoclonal antibody that specifically binds to human DLL4,
(a) CDRアミノ酸配列CDR1 (SEQ ID NO: 1)、CDR2 (SEQ ID NO: 2、SEQ ID NO: 3、またはSEQ ID NO: 4)、およびCDR3 (SEQ ID NO: 5) を含む、重鎖可変領域、ならびに(a) A heavy chain comprising CDR amino acid sequences CDR1 (SEQ ID NO: 1), CDR2 (SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4), and CDR3 (SEQ ID NO: 5). The chain variable region, and
(b) CDRアミノ酸配列CDR1 (SEQ ID NO: 9)、CDR2 (SEQ ID NO: 10)、およびCDR3 (SEQ ID NO: 11) を含む、軽鎖可変領域(b) Light chain variable region comprising CDR amino acid sequences CDR1 (SEQ ID NO: 9), CDR2 (SEQ ID NO: 10), and CDR3 (SEQ ID NO: 11)
を含み、0.01μMまたはそれ未満のK0.01 μM or less K DD でDLL4に結合することができる、モノクローナル抗体。Monoclonal antibody that can bind to DLL4. 重鎖可変領域がCDRアミノ酸配列CDR1 (SEQ ID NO: 1)、CDR2 (SEQ ID NO: 3)、およびCDR3 (SEQ ID NO: 5) を含み、軽鎖可変領域がCDRアミノ酸配列CDR1 (SEQ ID NO: 9)、CDR2 (SEQ ID NO: 10)、およびCDR3 (SEQ ID NO: 11) を含む、請求項6または7記載の抗体。The heavy chain variable region comprises the CDR amino acid sequence CDR1 (SEQ ID NO: 1), CDR2 (SEQ ID NO: 3), and CDR3 (SEQ ID NO: 5), and the light chain variable region comprises the CDR amino acid sequence CDR1 (SEQ ID NO. 8. The antibody of claim 6 or 7, comprising NO: 9), CDR2 (SEQ ID NO: 10), and CDR3 (SEQ ID NO: 11). SEQ ID NO: 6、SEQ ID NO: 7、またはSEQ ID NO: 8に対し少なくとも90%の配列同一性を有する重鎖可変領域を含む、請求項6〜8のいずれか一項記載の抗体。9. The antibody of any one of claims 6-8, comprising a heavy chain variable region having at least 90% sequence identity to SEQ ID NO: 6, SEQ ID NO: 7, or SEQ ID NO: 8. SEQ ID NO: 12に対し少なくとも90%の配列同一性を有する軽鎖可変領域を含む、請求項6〜9のいずれか一項記載の抗体。10. The antibody of any one of claims 6 to 9, comprising a light chain variable region having at least 90% sequence identity to SEQ ID NO: 12. ATCCに寄託され寄託番号PTA-8670を持つハイブリドーマにより産生される21M18抗体内に含有される重鎖可変領域CDRアミノ酸配列および軽鎖可変領域CDRアミノ酸配列を含有する、モノクローナル抗体であって、腫瘍成長を阻害することができる抗体。A monoclonal antibody comprising a heavy chain variable region CDR amino acid sequence and a light chain variable region CDR amino acid sequence contained within a 21M18 antibody produced by a hybridoma deposited with the ATCC and having deposit number PTA-8670, wherein the tumor growth Antibodies that can inhibit ATCCに寄託され寄託番号PTA 8427またはPTA 8425を持つプラスミドによりコードされる抗体と、ヒトDLL4への特異的結合について競合する、ヒト化抗体であって、腫瘍成長を阻害することができる抗体。A humanized antibody that competes for specific binding to human DLL4 with an antibody deposited with the ATCC and encoded by a plasmid having the deposit number PTA 8427 or PTA 8425, and that can inhibit tumor growth. ヒト化抗体である、請求項1〜11のいずれか一項記載の抗体。The antibody according to any one of claims 1 to 11, which is a humanized antibody. ヒト抗体である、請求項1〜11のいずれか一項記載の抗体。The antibody according to any one of claims 1 to 11, which is a human antibody. 二重特異性抗体である、請求項1〜14のいずれか一項記載の抗体。15. The antibody according to any one of claims 1 to 14, which is a bispecific antibody. IgG1抗体である、請求項1〜15のいずれか一項記載の抗体。The antibody according to any one of claims 1 to 15, which is an IgG1 antibody. IgG2抗体である、請求項1〜15のいずれか一項記載の抗体。The antibody according to any one of claims 1 to 15, which is an IgG2 antibody. ヒトDLL1またはヒトDLL3と交差反応しない、請求項1〜17のいずれか一項記載の抗体。The antibody according to any one of claims 1 to 17, which does not cross-react with human DLL1 or human DLL3. マウスDLL4と交差反応しない、請求項1〜18のいずれか一項記載の抗体。The antibody according to any one of claims 1 to 18, which does not cross-react with mouse DLL4. 約0.1μMまたはそれ未満のKAbout 0.1 μM or less K DD を有する、請求項1〜6および8〜19のいずれか一項記載の抗体。The antibody according to any one of claims 1 to 6 and 8 to 19. 請求項1〜20のいずれか一項記載の抗体および薬学的に許容される担体を含む、薬学的組成物。21. A pharmaceutical composition comprising the antibody according to any one of claims 1 to 20 and a pharmaceutically acceptable carrier. 癌を処置するための医薬の製造における、請求項1〜20のいずれか一項記載の抗体の使用。21. Use of an antibody according to any one of claims 1 to 20 in the manufacture of a medicament for treating cancer. 前記抗体が、固形腫瘍における癌幹細胞頻度を低下させる、請求項22記載の抗体の使用。23. Use of an antibody according to claim 22, wherein the antibody reduces the frequency of cancer stem cells in a solid tumor. 癌が、結腸癌、乳癌、肺癌、または膵臓癌である、請求項23記載の抗体の使用。24. Use of the antibody according to claim 23, wherein the cancer is colon cancer, breast cancer, lung cancer, or pancreatic cancer. 癌の処置が、前記抗体および第2の治療剤の投与を含む、請求項22〜24のいずれか一項記載の抗体の使用。25. Use of an antibody according to any one of claims 22 to 24, wherein the treatment of cancer comprises administration of the antibody and a second therapeutic agent. 第2の治療剤が化学療法剤または第2の抗体である、請求項25記載の抗体の使用。26. Use of the antibody of claim 25, wherein the second therapeutic agent is a chemotherapeutic agent or a second antibody. 第2の治療剤が抗VEGF抗体である、請求項26記載の抗体の使用。27. Use of an antibody according to claim 26, wherein the second therapeutic agent is an anti-VEGF antibody. 請求項1〜20のいずれか一項記載の抗体を発現する細胞。A cell that expresses the antibody according to any one of claims 1 to 20. 請求項1〜20のいずれか一項記載の抗体またはその可変領域をコードする、ポリヌクレオチド。A polynucleotide encoding the antibody or the variable region thereof according to any one of claims 1 to 20. SEQ ID NO: 13、SEQ ID NO: 14、SEQ ID NO: 15、またはSEQ ID NO: 16に対し少なくとも90%同一であるヌクレオチド配列を含む、請求項29記載のポリヌクレオチド。30. The polynucleotide of claim 29, comprising a nucleotide sequence that is at least 90% identical to SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, or SEQ ID NO: 16. SEQ ID NO: 13、SEQ ID NO: 14、SEQ ID NO: 15、またはSEQ ID NO: 16のヌクレオチド配列を含む、請求項29記載のポリヌクレオチド。30. The polynucleotide of claim 29 comprising the nucleotide sequence of SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, or SEQ ID NO: 16. 請求項29または30記載のポリヌクレオチドを含む、ベクター。A vector comprising the polynucleotide of claim 29 or 30.
JP2014043403A 2006-09-29 2014-03-06 Compositions and methods for diagnosis and treatment of cancer Expired - Fee Related JP5997194B2 (en)

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US84790406P 2006-09-29 2006-09-29
US60/847,904 2006-09-29
US88626007P 2007-01-23 2007-01-23
US60/886,260 2007-01-23
US94254207P 2007-06-07 2007-06-07
US60/942,542 2007-06-07

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